Mpox and Chickenpox Coinfection: Case Series From Southern Nigeria

Abstract

Mpox is a disease caused by the mpox virus (MPXV), an orthopox virus that resembles the smallpox virus. It was first isolated from humans in 1970 following which several outbreaks and sporadic cases were reported in West and Central Africa [1–3]. Mpox reemerged in Nigeria in 2017 with an outbreak that involved several states and has remained endemic in the country [4, 5].

Before the 2022 multicountry mpox outbreak, which led the World Health Organization (WHO) to declare it a public health emergency of international concern in July 2022, it was scarcely reported outside the endemic African regions. Although this outbreak had ended, mpox in July 2023 still posed a moderate global risk with 88 288 laboratory-confirmed cases and 149 deaths involving 112 countries/areas/territories [6]. Africa accounted for 1802 laboratory-confirmed cases and 21 deaths, representing 2% of cases and 14% of deaths globally [6].

While limited reports have shown concomitant varicella-zoster virus (VZV) and MPXV coinfection in the endemic African subregion [1, 7], there is evidence that VZV and MPXV cocirculate in these endemic regions [1, 2]. This coinfection of VZV and MPX is associated with severe mpox presentation and also poses diagnostic dilemmas in clinically distinguishing both conditions due to similar presentations [2, 8, 9]. In Nigeria, the burden/impact of chickenpox is unexplored as it is not a notifiable disease and its vaccine is not integrated into the national program on immunization. The paucity of literature on the disease dynamics in mpox and chickenpox coinfected individuals calls for an improved understanding of the epidemiology and clinical characteristics of both conditions, especially in settings of high endemicity. Here, we report case series of mpox and chickenpox coinfection observed in Nigerian patients during a period that included the 2022 global mpox outbreak. We describe the epidemiology, clinical characteristics, and disease outcome in this cohort and compare the characteristics of mpox-chickenpox coinfected and mpox monoinfected patients.

METHODS

Study Design, Study Site, and Study Population

We conducted a retrospective cohort study on confirmed mpox cases, identifying those with chickenpox coinfection managed between 1 January 2022 and 31 March 2023 in 6 states in Southern Nigeria. Infectious diseases physicians in 6 tertiary hospitals who served as mpox state case managers participated in the study. Hospitals studied were University of Nigeria Teaching Hospital, Ituku/Ozalla, Enugu State, Federal University Teaching Hospital, Owerri, Imo State, Nnamdi Azikwe University Teaching Hospital, Nnewi, Anambra State, University of Uyo Teaching Hospital, Uyo, Akwa Ibom State, Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi State, and University of Port-Harcourt Teaching Hospital, Port-Harcourt, Rivers State. These hospitals are referral centers for their states and each operates the largest infectious diseases centers within these states, hence their selection.

All persons that presented to the above hospitals who met the criteria for suspected mpox cases per the Nigeria Centre for Disease Control (NCDC) were eligible for enrollment. NCDC guidelines for mpox case definition applied [5]: (1) suspected case, an acute febrile illness with compatible clinical features that is followed by the development of a rash in a few days; (2) confirmed case: a clinically compatible case with laboratory confirmation; and (3) probable case: a clinically compatible case with epidemiological link to a confirmed case but no laboratory confirmation. Mpox and chickenpox were confirmed using real-time polymerase chain reaction (RT-PCR) assay of swab and/or crust samples at the National Reference Laboratory of the NCDC, Abuja Nigeria [5]. Mpox and chickenpox coinfection was defined as concomitant RT-PCR positivity to MPXV and VZV using swab and/or crust samples. Participants whose swab or crust sample RT-PCR results tested positive for MPXV irrespective of the VZV results were included in the study while those with negative or inconclusive MPXV RT-PCR results were excluded.

Data Collection

Data was extracted using the WHO mpox case reporting form version 3 dated December 2022, which included demographics, medical history, clinical presentation, and laboratory information. Additionally, vital signs documented at presentation (axillary temperature, respiratory rate, oxygen saturation), complications, and outcomes were noted, as were summary statistics from the medical records of individual hospitals. Patients were managed per NCDC guidelines [5]. Management outcomes were categorized as hospital admission (outpatient vs hospitalized) or survival (survived vs died). Duration of hospitalization was the number of days until discharge/death, which ever came first.

Ethical Considerations

Ethical approval was obtained from local institutional review boards of all sites involved in the study. Patient consent was not required as it was a retrospective cohort study, hence there was no direct contact with patients for the purpose of the study.

Statistical Analysis

Data analysis was descriptive using SPSS version 25.0 analytical software. Continuous variables were described as mean ± SD when normally distributed or median (interquartile range [IQR]) when skewed. Categorical variables were described as counts and frequencies. For comparing mpox-chickenpox coinfected and mpox monoinfected cases, variables of interest were dichotomized and subsequently compared using the χ² test or Fisher exact test when appropriate. P value < .05 was considered statistically significant.

RESULTS

Of 94 suspected cases of mpox, 56 (60.0%) were laboratory-confirmed, 3 (3.1%) were probable, and 35 (37.2%) had negative MPXV RT-PCR tests. Sixteen (28.6%) persons with RT-PCR–confirmed mpox had chickenpox coinfection (Supplementary Figure 1). The majority (37, 66.1%) presented in the wet season of April to October with the peak (13) in September while 19 (33.9%) occurred in the dry season. Persons aged 2–55 years were affected with a median age of 29 years (IQR, 20–37) years). Table 1 shows young adults aged 18–35 years (37, 66.1%) were the most affected age group. There were 24 (60.7%) males, 7 (12.5%) persons identified as either bisexual or men who have sex with men (MSM) while 17 of 40 (42.5%) patients with available sexual history had multiple sexual partners within the last month. Contact with suspected case was reported in 21 (37.5%), while 1 (1.8%) had contact with wildlife. Only 3 (5.4%) had travelled to an area reporting mpox.

Table 1 shows that most patients developed a fever (52, 92.9%) while all patients had an itchy rash which was generalized and started on the face in 34 (60.7%). Other frequently reported symptoms were headache 39 (69.6%), myalgia 37 (66.1%), and fatigue 30 (53.6%). Of the 54 patients with known human immunodeficiency virus (HIV) status, 13 (23.2%) were people with HIV (PWH). Of the PWH, viral load determined within the year was available for only 1, who was HIV suppressed (undetectable). CD4 count was available for 6 others; 4 of these had qualitative CD4 counts below 200 cells/mm³. The known absolute CD4 counts were 700 cells/mm³, 78 cells/mm³, and 74 cells/mm³. Three (5.4%) had diabetes, 1 of whom was PWH. Two women were pregnant.

The median duration of illness before presentation was 7 days (IQR, 5–14 days). The mean temperature at presentation was 37.5°C ± 0.9°C. Skin lesions were variable with pustules (82.1%) and vesicles (66.1%) commonly seen. Lymphadenopathy was observed in 20 (46.3%). All patients received individualized supportive care: antipyretics (acetaminophen), antihistamine, and fluid therapy. Nearly all (52, 92.9%) received empirical antibiotics. Commonly administered antibiotics were amoxicillin-clavulanic acid (27 of 52, 51.9%) and ceftriaxone (7 of 52, 13.5%). Thirty-seven patients (66.1%) were hospitalized based on physicians’ assessment of severe disease, of whom 18 (32.1%) developed complications with skin sepsis the commonest (15 of 18, 83.3%). Other reported complications were pneumonia and acute urinary retention in a female. The median duration of hospitalization was 14 days (IQR, 9–22 days). Five (8.9%) persons died.

Table 2 shows that as compared to patients with mpox monoinfection, mpox-chickenpox coinfected patients were significantly more likely to report muscle pain (87.5% vs 57.5%, P = .032), sore throat (68.8% vs 30.0%, P = .008), fatigue (75.0% vs 45.0%, P = .042), and complications (56.3% vs 22.5%, P = .015). In the coinfected group, 1 of the deceased patients was a PWH with CD4 of 78 cells/mm³. He died from sepsis with a wound focus that yielded Pseudomonas spp. The other also died from sepsis with a pulmonary focus. Among those coinfected that survived, the average time to resolution of skin lesion was 20 (IQR,16–24) days.

DISCUSSION

We describe, from a cohort of laboratory-confirmed cases of mpox, a case series of 28.6% of patients coinfected with chickenpox during the 2022 global mpox outbreak. This compares to 27% seen among 33 suspected mpox cases in North-East Nigeria but differs from much lower rates of 0.7% and 13% reported in Congo [2, 3, 10]. This high coinfection rate is concerning for severe clinical presentation, as highlighted by Ogoina et al [11]. We observed that adults aged 18–35 years (66.1%) were most affected by mpox with only 5 persons (8.9%) aged ≤17 years. This differs from earlier studies in Congo where children were predominantly affected [2, 3, 12]. These varied prevalence and age characteristics may be due to changing epidemiological trends. Earlier studies may have found children more susceptible to mpox as adults might have undergone smallpox vaccination previously. This herd immunity for smallpox, which equally protects against mpox, has waned over time, creating susceptible youths. Furthermore, urbanization may see fewer children exposed to wildlife reservoirs, which can introduce MPXV into a population. The predominance of adults among chickenpox cases may reflect susceptibility of adult population due to absent immunity from non-vaccination.

Males were more affected than females, a finding similar to previous reports of male preponderance in mpox [2, 3, 10, 12]. While 12.5% of our participants self-identified as bisexual or MSM, the actual role of their sexual preference in mpox-chickenpox coinfection could not be explored by our study design. Notwithstanding, the high level of recent multiple sexual partners (42.5%) reported by our study participants supports the importance of sexual activity as a driver of mpox transmission, as has been suggested previously and corroborated by WHO during the 2022 global outbreak [13]. It is possible that some might have been unaware of their sexual partner's health, especially if transmission occurred in the prodrome before rash developed. Furthermore, 37.5% of participants had contact with a suspected mpox case, which agrees with previous observations that outbreaks in Nigeria have been mainly driven by human-to-human transmission [4, 14]. This is likely the case as immunization against varicella is not routine and mpox vaccine is not available in our country.

Nearly all participants (92.9%) received empirical antibiotics during the course of their management, which is concerning although justifiable as sepsis was a frequent complication. Despite these, the practice of antimicrobial stewardship is undermined by the absence of laboratory sepsis workup in most patients due to lack of a containment laboratory where a dedicated sepsis workup for patients with high-consequence infectious diseases can be performed, and financial constraints, which possibly culminated in the high rate of complications as antibiotics were largely empirical. Acyclovir-based therapy used to treat chickenpox was instituted in 30.4% of participants, possibly due to a low index of suspicion for chickenpox, which is not a surveillance-based disease in our environment, and the relatively long turnaround time of PCR results negating their clinical utility. Five participants died, 2 of whom were coinfected with chickenpox. One of these 2 coinfected participants was a severely immunosuppressed PWH, similar to a case reported previously [15]. Coinfection with chickenpox leading to severe illness and varicella pneumonia, which is not an uncommon complication of chickenpox, perhaps explains the death of the other participant. Although our study did not reveal any statistically significant association of death with coinfection, we observed that persons coinfected with chickenpox had a higher risk, with 4.4 times the odds, for developing complications compared to those with mpox monoinfection. Other findings significantly associated with coinfection were myalgia, sore throat, and fatigue, which are nonspecific. A relatively low frequency of lymphadenopathy (46.5%) was observed, which contradicts findings that have reported predominance of lymphadenopathy (35 of 40) [7]. It is unclear if the additional 13 cases in whom findings were unavailable will have influenced this observation. As mpox case managers, we learnt that chickenpox cocirculates in our environment due to absence of herd immunity, mpox diagnosis based on symptomatology is inadequate, and there is the need for heightened suspicion for coinfection due to the high risk for complications. In addition, there is a need to prioritize chickenpox surveillance, and mpox and chickenpox vaccine campaigns in Africa.

Our study is limited by its relatively small sample size, which made it difficult to conduct a multivariate analysis. Additionally, unavailable data on chickenpox exposure, the inability to assess the impact of antiviral therapy due to the lack of mpox-specific antivirals, and the limited data on acyclovir where indicated. Nevertheless, the strength of our study lies in the critical public health importance of characterizing the clinicoepidemiologic features of mpox-chickenpox in a resource-limited setting endemic for both conditions but with little or no access to vaccines in public health programs.

Supplementary Data

Supplementary materials are available at The Journal of Infectious Diseases online (http://jid.oxfordjournals.org/). Supplementary materials consist of data provided by the author that are published to benefit the reader. The posted materials are not copyedited. The contents of all supplementary data are the sole responsibility of the authors. Questions or messages regarding errors should be addressed to the author.

Notes

Acknowledgments. We acknowledge the efforts of the health care workers, disease surveillance and notification officers, state epidemiologists, State Directors of Public Health, State Ministry of Health, and Nigeria Centre for Disease Control staff amongst others who supported patient care or data collection in the mpox outbreak response.

Financial support. No financial support was received for this work.

Supplement sponsorship. This article appears as part of the supplement “Mpox: Challenges and Opportunities Following the Global 2022 Outbreak,” sponsored by the Centers for Disease Control and Prevention (Atlanta, GA).

References

Author notes